Biology of Depression - Neurotransmitters

Rashmi Nemade, Ph.D.

image by Patrick Hoesly (lic)Lots of research has been done on the causes of depression. We are now going to have a brief discussion of the many biological, psychological and social factors that have been identified as being related to major depressive disorder.

Biology of Depressive Disorders

You may have heard that depression is the result of a simple imbalance of brain chemicals. Although brain chemicals are certainly part of the cause, this explanation is too simple. Even just considering the biological dimension of depression, the brain has multiple layers of issues that are involved.

Neurochemistry

Neurotransmitters

The brain uses a number of chemicals as messengers to communicate with other parts of itself and within the nervous system. Nerve cells are the major type of cell in the nervous system. These are called neurons. They communicate through chemical messengers, called neurotransmitters. These messengers are released and received by the brain's many neurons. Neurons are constantly communicating with each other by exchanging neurotransmitters. This communication system is essential to all of the brain's functions.

A neuron has a cell body and a tail-like structure called an axon. Neurons are spaced apart by a tiny space called a synapse. In a simple scenario, one neuron (the sender) sends a neurotransmitter message across the synapse to the next neuron (the receiver). The receiver neuron is activated by whatever chemical it just received and communicates the signal down the chain to the next neuron. The receiving end of a neuron has receptors, which receive the chemical signals. When the perfect matching signal or neurotransmitter reaches its receptor across the tiny space, the receptor is activated. It then sends the message along to the next neuron by way of a neurotransmitter. For example, if someone has to go through many locked doors with each door being behind another locked door, the right key is needed. If the first door is opened with the right key, then the person can proceed to the next door with the next key and so on.

In music, it's not just the notes that make up a melody. It is also the spaces or rests between the notes that make each note stand out and be distinct. It's exactly the same with regard to neurotransmitters and synapses. There needs to be some quiet time between neurotransmitter messages for those messages to have any meaning. It is important that receptors be allowed to reset and deactivate between messages so that they can become ready to receive the next burst of neurotransmitters. In order to achieve this "resetting", the receptors relax and release their captured neurotransmitters back into the tiny space where about 90% of them get taken up again (in a process called reuptake) by the original sending neuron. The neurotransmitters are then repackaged and reused the next time a message needs to be sent across the synapse. Even though this seems like a complicated set of steps, this entire information transmission cycle occurs in the brain within in a matter of seconds. Any problem that interrupts the smooth functioning of this chain of chemical events can negatively impact both the brain and nervous system.

Depression has been linked to problems or imbalances in the brain, specifically with the neurotransmitters serotonin, norepinephrine, and dopamine. It is very difficult to actually measure the level of neurotransmitters in a person's brain and their activity. What we do know is that antidepressant medications, which are used to treat the symptoms of depression, are known to act upon these particular neurotransmitters and their receptors. We'll talk more about antidepressant medications in the treatment section of this center.

The neurotransmitter serotonin is involved in controlling many important bodily functions, including sleep, aggression, eating, sexual behavior, and mood. Serotonin is produced by serotonergic neurons. Current research suggests that a decrease in the production of serotonin by these neurons can cause depression in some people, and more specifically, a mood state that can cause some people to feel suicidal.

In the 1960s, the "catecholamine hypothesis" was a popular explanation for why people developed depression. This hypothesis suggested that a deficiency of the neurotransmitter norepinephrine (also known as noradrenaline) in certain areas of the brain was responsible for creating depressed mood. More recent research suggests that there is a group of people with depression who have low levels of norepinephrine. Autopsy studies show that people who have experienced multiple depressive episodes have fewer norepinephrinergic neurons than people who have no depressive history. However, research results also tell us that not all people experience mood changes in response to decreased norepinephrine levels. Some people who are depressed actually show more than normal within the neurons that produce norepinephrine. More current studies suggest that in some people, low levels of serotonin trigger a drop in norepinephrine levels, which then leads to depression.

Another line of research has investigated linkages between stress, depression, and norepinephrine. Norepinephrine helps our bodies to recognize and respond to stressful situations. Researchers suggest that people who are vulnerable to depression may have a norepinephrinergic system that doesn't handle the effects of stress very efficiently.

The neurotransmitter dopamine is also linked to depression. Dopamine plays an important role in controlling our drive to seek out rewards, as well as our ability to obtain a sense of pleasure. Low dopamine levels may, in part, explain why people with depression don't get the same sense of pleasure out of activities or people that they did before becoming depressed.

In addition, new studies are showing that other neurotransmitters such as acetylcholine, glutamate, and Gamma-aminobutyric acid (GABA) can also play a role in depressive disorders. More research is necessary to understand their role in depression's brain chemistry.